Association between Antibiotic Exposure and Systemic Immune Parameters in Cancer Patients Receiving Checkpoint Inhibitor Therapy

Mitchell S. von Itzstein, Amrit S. Gonugunta, Thomas Sheffield, Jade Homsi, Jonathan E. Dowell, Andrew Y. Koh, Prithvi Raj, Farjana Fattah, Yiqing Wang, Vijay S. Basava, Shaheen Khan, Jason Y. Park, Vinita Popat, Jessica M. Saltarski, Yvonne Gloria-Mccutchen, David Hsiehchen, Jared Ostmeyer, Yang Xie, Quan-zhen Li, Edward K. WakelandDavid E. Gerber

Research output: Contribution to journalArticlepeer-review

Abstract

Antibiotic administration is associated with worse clinical outcomes and changes to the gut microbiome in cancer patients receiving immune checkpoint inhibitors (ICI). However, the effects of antibiotics on systemic immune function are unknown. We, therefore, evaluated antibiotic exposure, therapeutic responses, and multiplex panels of 40 serum cytokines and 124 antibodies at baseline and six weeks after ICI initiation, with p < 0.05 and false discovery rate (FDR) < 0.2 considered significant. A total of 251 patients were included, of whom the 135 (54%) who received antibiotics had lower response rates and shorter survival. Patients who received antibiotics prior to ICI initiation had modestly but significantly lower baseline levels of nucleolin, MDA5, c-reactive protein, and liver cytosol antigen type 1 (LC1) antibodies, as well as higher levels of heparin sulfate and Matrigel antibodies. After ICI initiation, antibiotic-treated patients had significantly lower levels of MDA5, CENP.B, and nucleolin antibodies. Although there were no clear differences in cytokines in the overall cohort, in the lung cancer subset (53% of the study population), we observed differences in IFN-γ, IL-8, and macrophage inflammatory proteins. In ICI-treated patients, antibiotic exposure is associated with changes in certain antibodies and cytokines. Understanding the relationship between these factors may improve the clinical management of patients receiving ICI.

Original languageEnglish (US)
Article number1327
JournalCancers
Volume14
Issue number5
DOIs
StatePublished - Mar 1 2022

Keywords

  • Antibiotics
  • Antibodies
  • Biomarkers
  • Cancer
  • Cytokines
  • Efficacy
  • Immune checkpoint inhibitors
  • Immunotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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